Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation

OBJECTIVE: We recently demonstrated that vasopressin alone resulted in a poorer outcome in a pediatric porcine model of asphyxial cardiac arrest when compared with epinephrine alone or with epinephrine plus vasopressin in combination. Accordingly, this study was designed to differentiate whether the inferior effects of vasopressin in pediatrics were caused by the type of cardiac arrest. DESIGN: Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11 kg. INTERVENTIONS: After 8 mins of ventricular fibrillation and 8 mins of cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered. Six minutes after drug administration, a second respective bolus dose of 0.8 units/kg vasopressin, 200 microg/kg epinephrine, or a combination of 200 microg/kg epinephrine with 0.8 units/kg vasopressin was given. Defibrillation was attempted 20 mins after initiating cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem left ventricular myocardial blood flow 2 mins after each respective drug administration was 65 +/- 4 and 70 +/- 13 mL x min(-1) x 100 g(-1) in the vasopressin group; 83 +/- 42 and 85 +/- 41 mL x min(-1) x 100 g(-1) in the epinephrine group; and 176 +/- 32 and 187 +/- 29 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p <.006 after both doses of epinephrine-vasopressin vs. vasopressin and after the first dose of epinephrine-vasopressin vs. epinephrine, respectively). At the same times, mean +/- sem total cerebral blood flow was 73 +/- 3 and 47 +/- 5 mL x min(-1) x 100 g(-1) after vasopressin; 18 +/- 2 and 12 +/- 2 mL x min(-1) x 100 g(-1) after epinephrine; and 79 +/- 21 and 41 +/- 8 mL x min(-1) x 100 g(-1) after epinephrine-vasopressin (p <.025 after both doses of vasopressin and epinephrine-vasopressin vs. epinephrine). Five of six vasopressin-treated, two of six epinephrine-treated, and six of six epinephrine-vasopressin treated animals had return of spontaneous circulation (nonsignificant). CONCLUSIONS: In this pediatric porcine model of ventricular fibrillation, the combination of epinephrine with vasopressin during cardiopulmonary resuscitation resulted in significantly higher levels of left ventricular myocardial blood flow than either vasopressin alone or epinephrine alone. Both vasopressin alone and the combination of epinephrine with vasopressin, but not epinephrine alone, improved total cerebral blood flow during cardiopulmonary resuscitation. In stark contrast to asphyxial cardiac arrest, vasopressin alone or in combination with epinephrine appears to be of benefit after ventricular fibrillation in the pediatric porcine model.     

Effects of combined administration of vasopressin, epinephrine, and norepinephrine during cardiopulmonary resuscitation in pigs

OBJECTIVE: Synergistic effects of epinephrine and vasopressin may be of benefit during cardiopulmonary resuscitation. However, cerebral perfusion was decreased when epinephrine was combined with vasopressin compared with vasopressin alone. Although a combined infusion of norepinephrine and vasopressin improves hemodynamic variables compared with norepinephrine alone during sepsis, it is unknown whether norepinephrine in addition to vasopressin and epinephrine changes vital organ perfusion during cardiopulmonary resuscitation. DESIGN: Prospective, randomized animal study. SETTING:: University hospital research laboratory. SUBJECTS: Twenty-one domestic pigs. INTERVENTIONS: After 4 mins of ventricular fibrillation and 3 mins of basic life support, the pigs were randomly assigned to receive either 200 microg/kg epinephrine, 0.4 units/kg vasopressin alone, or 45 microg/kg norepinephrine plus 45 microg/kg epinephrine plus 0.4 units/kg vasopressin before defibrillation. MEASUREMENTS AND MAIN RESULTS: Organ perfusion was determined by radiolabeled microspheres. Myocardial blood flow (mean +/- sem) before and 90 secs and 5 mins after drug administration was 8 +/- 2, 25 +/- 6, and 7 +/- 1 mL/min/100 g after high-dose epinephrine, 12 +/- 1, 75 +/- 7, and 60 +/- 10 mL/min/100 g after vasopressin, and 9 +/- 2, 95 +/- 26, and 46 +/- 15 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). At the same time points, cerebral blood flow was 8 +/- 2, 23 +/- 3, and 17 +/- 3 mL/min/100 g after epinephrine, 11 +/- 3, 55 +/- 7, and 52 +/- 7 mL/min/100 g after vasopressin, and 11 +/- 4, 67 +/- 13, and 53 +/- 12 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). Two of seven animals in the epinephrine group, four of seven animals in the vasopressin/epinephrine/norepinephrine group, and seven of seven animals in the vasopressin group could be successfully resuscitated (p < .05 vasopressin vs. epinephrine). CONCLUSIONS: Vasopressin with or without epinephrine and norepinephrine resulted in higher myocardial and cerebral perfusion than epinephrine alone, but there was no benefit in adding norepinephrine to vasopressin and epinephrine with regard to cardiac and cerebral blood flow during cardiopulmonary resuscitation.     

Vasopressin decreases endogenous catecholamine plasma concentrations during cardiopulmonary resuscitation in pigs

OBJECTIVE: The purpose of this study was to evaluate the effect of vasopressin vs. saline placebo on catecholamine plasma concentrations during cardiopulmonary resuscitation (CPR). DESIGN: Prospective, randomized laboratory investigation by using an established porcine CPR model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Sixteen domestic pigs. INTERVENTIONS: After 15 mins of untreated cardiac arrest and 3 mins of CPR, 16 pigs were randomized to be treated with either 0.8 U/kg vasopressin (n = 8) or placebo (normal saline; n = 8). Arterial epinephrine and norepinephrine plasma concentrations were sampled at prearrest, after 1.5 mins of chest compressions, and at 1.5 mins and 5 mins after drug administration during CPR. MEASUREMENTS AND MAIN RESULTS: In comparison with placebo pigs at 1.5 and 5 mins after drug administration, animals resuscitated with vasopressin had significantly (p < .01) higher mean +/- SEM left ventricular myocardial (131+/-27 vs. 10+/-1 mL x mins(-1) x 100 g(-1) and 62+/-13 vs. 9+/-2 mL x mins(-1) x 100 g(-1)); total cerebral (90+/-8 vs. 14+/-3 mL x mins(-1) x 100 g(-1) and 51+/-4 vs. 12+/-2 mL x mins(-1) x 100 g(-1)); and adrenal gland perfusion (299+/-36 vs. 38+/-7 mL x mins(-1) x 100 g(-1) and 194+/-23 vs. 29+/-5 mL x mins(-1) x 100 g(-1)). Significantly lower mean +/- SEM epinephrine concentrations in the vasopressin pigs compared with the placebo group were measured 1.5 mins and 5 mins after drug administration, (24167+/-7919 vs. 80223+/-19391 pg/mL [p < .01] and 8346+/-1454 vs. 71345+/-10758 pg/mL [p < .01]). Mean +/- SEM norepinephrine plasma concentrations in the vasopressin animals in comparison with placebo were at 1.5 and 5 mins after drug administration significantly lower (41729+/-13918 vs. 82756+/-9904 pg/mL [p = .01] and 10642+/-3193 vs. 62170+/-8797 pg/mL [p < .01]). CONCLUSIONS: Administration of vasopressin during CPR resulted in significantly superior vital organ blood flow, but significantly decreased endogenous catecholamine plasma concentrations when compared with placebo.     

Comparison of epinephrine with vasopressin on bone marrow blood flow in an animal model of hypovolemic shock and subsequent cardiac arrest

OBJECTIVE: The intraosseous route is an emergency alternative for the administration of drugs and fluids if vascular access cannot be established. However, in hemorrhagic shock or after vasopressors are given during resuscitation, bone marrow blood flow may be decreased, thus impairing absorption of intraosseously administered drugs. In this study, we evaluated the effects of vasopressin vs. high-dose epinephrine in hemorrhagic shock and cardiac arrest on bone marrow blood flow. DESIGN: Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SETTING: University hospital laboratory. SUBJECTS: Fourteen pigs weighing 30 +/- 3 kg. INTERVENTIONS: Radiolabeled microspheres were injected to measure bone marrow blood flow during a prearrest control period and during hypovolemic shock produced by rapid hemorrhage of 35% of the estimated blood volume. In the second part of the study, ventricular fibrillation was induced; after 4 mins of untreated cardiac arrest and 4 mins of standard cardiopulmonary resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 6) or 0.8 units/kg vasopressin (n = 6) was administered. Defibrillation was attempted 2.5 mins after drug administration, and blood flow was assessed again at 5 and 30 mins after successful resuscitation. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem bone marrow blood flow decreased significantly during induction of hemorrhagic shock from 14.4 +/- 4.1 to 3.7 +/- 1.8 mL.100 g-1.min-1 in the vasopressin group and from 18.2 +/- 4.0 to 5.2 +/- 1.0 mL.100 g-1.min-1 in the epinephrine group (p =.025 in both groups). Five minutes after return of spontaneous circulation, mean +/- sem bone marrow blood flow was 3.4 +/- 1.1 mL.100 g-1.min-1 after vasopressin and 0.1 +/- 0.03 mL.100 g-1.min-1 after epinephrine (p =.004 for vasopressin vs. epinephrine). At the same time, bone vascular resistance was significantly (p =.004) higher in the epinephrine group when compared with vasopressin (1455 +/- 392 vs. 43 +/- 19 mm Hg. mL-1.100 g.min, respectively). CONCLUSIONS: Bone blood flow responds actively to both the physiologic stress response of hemorrhagic shock and vasopressors given during resuscitation after hypovolemic cardiac arrest. In this regard, bone marrow blood flow after successful resuscitation was nearly absent after high-dose epinephrine but was maintained after high-dose vasopressin. These findings emphasize the need for pressurized intraosseous infusion techniques, because bone marrow blood flow may not be predictable during hemorrhagic shock and drug therapy.     

Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs

OBJECTIVE: Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen domestic pigs. INTERVENTIONS: After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS: Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p < .05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003). CONCLUSIONS: Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.     

Effect of phased chest and abdominal compression-decompression cardiopulmonary resuscitation on myocardial and cerebral blood flow in pigs

OBJECTIVE: This study was designed to assess the effects of a phased chest and abdominal compression-decompression cardiopulmonary resuscitation (CPR) device, Lifestick, vs. standard CPR on vital organ blood flow in a porcine CPR model. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital research laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation, either the Lifestick CPR device (n = 6) or standard CPR (n = 6) was started and maintained for an additional interval of 6 mins before attempting defibrillation. MEASUREMENTS AND MAIN RESULTS: During CPR, but before epinephrine, use of the Lifestick CPR device resulted in significantly higher (p < .05) mean (+/- SD) coronary perfusion pressure (23+/-9 vs. 10+/-7 mm Hg), cerebral perfusion pressure (29+/-11 vs. 18+/-10 mm Hg), mean arterial pressure (49+/-10 vs. 36+/-13 mm Hg), end-tidal carbon dioxide (32+/-11 vs. 20+/-7 mm Hg), left ventricular myocardial blood flow (44+/-19 vs. 19+/-12 mL x min(-1) x 100 g(-1)), and total cerebral blood flow (29+/-10 vs. 14+/-12 mL x min(-1) x 100 g(-1)). After 45 microg/kg epinephrine, hemodynamic and vital organ blood flow variables increased to comparable levels in both groups. CONCLUSIONS: Compared with standard CPR, the Lifestick CPR device increased significantly hemodynamic variables and vital organ blood flow during CPR before epinephrine administration.     

Effects of vasopressin and epinephrine on splanchnic blood flow and renal function during and after cardiopulmonary resuscitation in pigs

OBJECTIVE: To compare the effects of vasopressin versus epinephrine on splanchnic blood flow during and after cardiopulmonary resuscitation (CPR), and to evaluate the effects of these vasopressors on renal function in the postresuscitation phase. DESIGN: Prospective, randomized laboratory investigation using an established porcine CPR model with instrumentation for continuous measurement of splanchnic and renal blood flow. SETTING: University hospital experimental laboratory. SUBJECTS: A total of 12 anesthetized, 12- to 16-wk-old domestic pigs weighing 30-35 kg. INTERVENTIONS: After 4 mins of cardiac arrest, and 3 mins of CPR, 12 pigs were randomly assigned to receive either 0.4 units/kg vasopressin (n = 6) or 45 microg/kg epinephrine (n = 6). Defibrillation was performed 5 mins after drug administration; all animals were observed for 6 hrs after return of spontaneous circulation (ROSC). MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM superior mesenteric artery blood flow was significantly (p < .05) lower after vasopressin compared with epinephrine at 90 secs after drug administration (13+/-3 vs. 129+/-33 mL/min); at 5 mins after drug administration (31+/-18 vs. 155+/-39 mL/min); at 5 mins after ROSC (332+/-47 vs. 1087+/-166 mL/min); and at 15 mins after ROSC (450+/-106 vs. 1130+/-222 mL/min); respectively. Mean +/- SEM left renal and hepatic artery blood flow after ROSC was comparable in both groups ranging between 120-290 mL/min (renal blood flow), and 150-360 mL/min (hepatic blood flow), respectively. Median urine output after ROSC showed no difference between groups, and highest values (180-220 mL/hr) were observed in the first 60 mins after ROSC. Median calculated glomerular filtration rate showed no difference between groups with values ranging between 30 and 80 mL/min in the postresuscitation phase. Calculated fractional sodium excretion and osmolar relationship between urea and plasma indicated no evidence for renal tubular dysfunction. CONCLUSIONS: In the early postresuscitation phase, superior mesenteric blood flow was temporarily impaired by vasopressin in comparison with epinephrine. With respect to renal blood flow and renal function after ROSC, there was no difference between either vasopressor given during CPR. Vasopressin given during CPR did not result in an antidiuretic state in the postresuscitation phase.     

Arginine vasopressin,but not epinephrine,improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs

OBJECTIVE: Epinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DESIGN: Prospective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SETTING: University hospital laboratory. SUBJECTS: A total of 21 pigs weighing 32 +/- 3 kg. INTERVENTIONS: The anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean +/- sem loss of 40% +/- 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units.kg-1.min-1, n = 7), or epinephrine (45 microg/kg and 5 microg.kg(-1).min(-1), n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem arterial blood pressure at 2.5 and 10 mins was significantly (p <.001) higher after vasopressin vs. epinephrine vs. saline placebo (82 +/- 14 vs. 23 +/- 4 vs. 11 +/- 3 mm Hg, and 42 +/- 4 vs. 10 +/- 5 vs. 6 +/- 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p <.01) higher when compared with epinephrine or saline placebo (9 +/- 5 vs. 121 +/- 3 vs. 54 +/- 22 mL/min and 150 +/- 20 vs. 31 +/- 17 vs. 0 +/- 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo-treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p <.01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. CONCLUSIONS: Vasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.     

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.     

Pulmonary gas exchange after cardiopulmonary resuscitation with either vasopressin or epinephrine

OBJECTIVE: It is well established that epinephrine administered during cardiopulmonary resuscitation results in pulmonary gas exchange disturbances. It is uncertain how vasopressin affects gas exchange after cardiopulmonary resuscitation. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty domestic pigs. INTERVENTIONS: Animals were subjected to ventricular fibrillation and cardiopulmonary resuscitation by using either vasopressin or epinephrine. Hemodynamic and pulmonary gas exchange (multiple inert gas elimination technique) variables were recorded before cardiopulmonary resuscitation and 10, 30, 60, and 120 mins after return of spontaneous circulation when either epinephrine (control) or vasopressin was used. MEASUREMENTS AND MAIN RESULTS: At 10 mins after return of spontaneous circulation, blood flow to low V /Q lung units was increased in animals treated with epinephrine (17.8 +/- 6 vs. 2.6 +/- 3%, mean +/- sd, p<.01). Resulting carbon dioxide elimination was impaired in animals treated with epinephrine but not in animals treated with vasopressin (PaCO2, 55 +/- 2 vs. 46 +/- 4 torr, p<.05). Thirty minutes after return of spontaneous circulation, blood flow to lung units with a normal VA /Q ratio was reduced in animals treated with epinephrine (79 +/- 1 vs. 84 +/- 12%, p<.05), resulting in a depressed PaO2 (147 +/- 4 vs. 127 +/- 10 torr, p<.05). CONCLUSION: Vasopressin compared with epinephrine for cardiopulmonary resuscitation resulted in better gas exchange variables in the early postresuscitation phase.     

Hemodynamic and metabolic effects of epinephrine during cardiopulmonary resuscitation in a pig model.

BACKGROUND AND METHODS: This study was designed to assess the effect of epinephrine during cardiopulmonary resuscitation (CPR) on left ventricular myocardial blood flow, systemic oxygen delivery and consumption, and on plasma glucose and lactate concentrations. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 mins of ventricular fibrillation, and 3 mins of open-chest CPR. Left ventricular myocardial blood flow was measured with radiolabeled microspheres. Plasma catecholamine concentrations were measured by high-pressure liquid chromatography. RESULTS: During open-chest CPR, mean (+/- SD) values of left ventricular myocardial blood flow before, 90 secs, and 5 mins following drug administration were 49 +/- 10, 46 +/- 12, 43 +/- 15 mL/min/100 g, respectively, in the control group, and 52 +/- 12, 118 +/- 21, 84 +/- 28 mL/min/100 g, respectively, in the epinephrine group (p less than .05 at 90 secs and 5 mins). At the same time points, mean (+/- SD) oxygen delivery indices were 7.7 +/- 3.0, 6.0 +/- 2.1, 6.5 +/- 2.7 mL/min/kg in the control group and 7.6 +/- 2.5, 5.3 +/- 2.1, 5.5 +/- 1.9 mL/min/kg in the epinephrine group (nonsignificant). Mean oxygen consumption indices were 5.8 +/- 2.4, 4.6 +/- 1.6, 5.2 +/- 2.6 mL/min/kg in the control group and 5.4 +/- 1.6, 4.2 +/- 1.6, 4.4 +/- 1.4 mL/min/kg in the epinephrine group (nonsignificant). During CPR and before epinephrine administration, arterial plasma epinephrine concentrations increased from prearrest values of 0.77 +/- 0.70 to 62.1 +/- 48.7 micrograms/L, and plasma norepinephrine concentrations increased from 0.28 +/- 0.32 to 104.3 +/- 57.1 micrograms/L. After administered epinephrine, there was an additional increase to 271 +/- 83 micrograms/L at 90 secs in arterial plasma epinephrine, but no important alteration in the plasma norepinephrine concentration. At no time point could we find a clinically important difference in plasma glucose or lactate concentrations between the two groups. CONCLUSIONS: At a dose of 45 micrograms/kg, epinephrine caused an increase in left ventricular myocardial blood flow after a total of 8 mins of cardiac arrest, including 3 mins of CPR, while not altering systemic oxygen delivery and consumption, plasma glucose, or lactate concentrations.     

Combination drug therapy with vasopressin,adrenaline (epinephrine) and nitroglycerin improves vital organ blood flow in a porcine model of ventricular fibrillation

There is increasing evidence that the combination of epinephrine (adrenaline) with vasopressin may be superior to either epinephrine or vasopressin alone for treatment of cardiac arrest. However, the optimal combination, and dosage of cardiovascular drugs to minimize side effects, and to improve outcome has yet to be found. We therefore evaluated whether the combination of vasopressin plus epinephrine plus nitroglycerin (EVN), would improve vital organ blood flow during cardiopulmonary resuscitation (CPR) when compared with epinephrine (EPI) alone. After 4 min of ventricular fibrillation (VF) and 4 min of standard CPR, pigs were randomized to the combination of epinephrine (45 microg/kg) plus vasopressin (0.4 U/kg) plus nitroglycerin (7.5 microg/kg; n=12), or epinephrine (40 microg/kg; n=12) alone. Cerebral and myocardial blood flow was measured with radiolabeled microspheres. Defibrillation was attempted after 19 min of VF including 15 min of CPR. Mean+/-SEM coronary perfusion pressures were significantly (P < 0.01) higher 5 min after EVN vs. EPI alone (34+/-3 vs. 24+/-3 mmHg, respectively). At the same time, mean+/-SEM left ventricular, and global cerebral blood flow was also significantly (P < 0.05) higher after EVN vs. EPI alone (0.78+/-0.11 vs. 0.48+/-0.08 ml/min/g; and 0.37+/-0.05 vs. 0.22+/-0.0 3 ml/min/g, respectively). Spontaneous circulation was restored in 11 of 12 animals in the EVN group vs. 6 of 12 swine after EPI alone (P = N.S.). In conclusion, the combination of EVN significantly improved vital organ blood flow during CPR compared with EPI alone. Addition of nitroglycerin to the combination of low dose epinephrine with vasopressin during cardiac arrest may be beneficial.     

Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation

OBJECTIVES: Both epinephrine and vasopressin increase aortic and carotid arterial pressure when administered during cardiopulmonary resuscitation. However, we recently demonstrated that epinephrine reduces cerebral cortical microcirculatory blood flow. Accordingly, we compared the effects of nonadrenergic vasopressin with those of epinephrine on cerebral cortical microvascular flow together with cortical tissue Po2 and Pco2 as indicators of cortical tissue ischemia. DESIGN: Randomized, prospective animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Domestic pigs. MEASUREMENTS AND MAIN RESULTS: The tracheae of ten domestic male pigs, weighing 40 +/- 2 kg, were noninvasively intubated, and the animals were mechanically ventilated. A frontoparietal bilateral craniotomy was created. Microcirculatory blood flow was quantitated with orthogonal polarization spectral imaging. Blood flow velocity in pial and cortical penetrating vessels measuring <20 microm was graded from 0 (no flow) to 3 (normal). Cerebral cortical tissue carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were measured concurrently using miniature optical sensors. Ventricular fibrillation, induced with an alternating current delivered to the right ventricular endocardium, was untreated for 3 mins. Animals were then randomized to receive central venous injections of equipressor doses of epinephrine (30 microg/kg) or vasopressin (0.4 units/kg) at 1 min after the start of cardiopulmonary resuscitation. After 4 mins of cardiopulmonary resuscitation, defibrillation was attempted. Spontaneous circulation was restored in each animal. However, postresuscitation microvascular flows and Pbo2 were greater and Pbco2 less after vasopressin when compared with epinephrine. We observed that a significantly greater number of cortical microvessels were perfused after vasopressin. CONCLUSIONS: Cortical microcirculatory blood flow was markedly reduced after epinephrine, resulting in a greater severity of brain ischemia after the restoration of spontaneous circulation in contrast to the more benign effects of vasopressin.     

Selective aortic arch perfusion with hemoglobin-based oxygen carrier-201 for resuscitation from exsanguinating cardiac arrest in swine.

OBJECTIVE: The prospects for resuscitation after blunt traumatic cardiac arrest are dismal. Selective aortic arch perfusion (SAAP) with a hemoglobin-based oxygen carrier (HBOC-201) offers a potentially effective therapy. This study evaluated the acute cardiovascular and metabolic effects of SAAP with HBOC-201 in an exsanguination model of cardiac arrest. DESIGN: Randomized, controlled, laboratory investigation. SETTING: University research laboratory. SUBJECTS: Domestic swine, 25-39 kg. INTERVENTIONS: Partial resection of four liver lobes rapidly led to profound hemorrhagic shock and subsequent cardiac arrest at 10-13 mins. At 15 mins, swine were randomized to receive either SAAP with oxygenated lactated Ringer's (LR) solution (n = 6) or SAAP with oxygenated HBOC-201 (n = 6) at a rate of 10 mL x kg(-1) x min(-1) until return of spontaneous circulation with a mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved. Epinephrine (0.005 mg/kg) was given via intra-aortic route every 30 secs as needed to promote return of spontaneous circulation beginning at 18 mins after onset of liver injury (3 mins after beginning SAAP). MEASUREMENTS AND MAIN RESULTS: Mean aortic pressure, cardiac output, total blood loss, and time of arrest were similar for both groups before SAAP therapy. In the SAAP-HBOC group, return of spontaneous circulation with a sustained mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved in six of six swine at 1.9 +/- 0.3 mins of SAAP, and none of these swine required epinephrine. In the SAAP-LR group, no swine (from a total of six) achieved return of spontaneous circulation before intra-aortic epinephrine administration, and only two of six swine had brief return of spontaneous circulation with an mean aortic pressure of 60 mm Hg (8.0 kPa) after intra-aortic epinephrine that was sustained for <10 mins. One-hour survival was five of six in the SAAP-HBOC group and none of six in the SAAP-LR group (p <.05, Fisher's exact test). CONCLUSION: SAAP with oxygenated HBOC-201 rapidly restored viable cardiovascular function after exsanguinating cardiac arrest in this swine model of liver injury with profound hemorrhagic shock.     

Effects of vasopressin on adrenal gland regional perfusion during experimental cardiopulmonary resuscitation

OBJECTIVE: Despite the important role of the adrenal gland during cardiac arrest, little is known about changes in the adrenal medullary or cortical blood flow in this setting. This study was designed to assess regional adrenal gland perfusion in the medulla and cortex during cardiopulmonary resuscitation (CPR), and after administration of adrenaline (epinephrine) versus vasopressin versus saline placebo. METHODS: After 4 min of untreated ventricular fibrillation, and 3 min of basic life support CPR, 19 animals were randomly assigned to receive either vasopressin (0.4 U/kg; n=7), adrenaline (45 microg/kg; n=6) or saline placebo (n=6), respectively. Haemodynamic variables, adrenal, and renal blood flow were measured after 90 s of CPR, and 90 s and 5 min after drug administration. RESULTS: All values are given as mean+/-S.E.M. Blood flow in the adrenal medulla was significantly higher 90 s after adrenaline when compared with saline placebo in the right adrenal medulla (210+/-14 vs. 102+/-5 ml/min per 100 mg), and in the left adrenal medulla (218+/-14 vs. 96+/-3 ml/min per 100 mg). Blood flow in the adrenal medulla was significantly higher 90 s and 5 min after vasopressin when compared with adrenaline in the right (326+/-22 mg vs. 210+/-14 ml/min per 100 mg, and 297+/-17 vs. 103+/-5 ml/min per 100 mg), and in the left medulla (333+/-25 vs. 218+/-14 ml/min per 100 mg, and 295+/-14 vs. 111+/-7 ml/min per 100 mg). Ninety seconds and five minutes after vasopressin, and 90 s after adrenaline, adrenal cortex blood flow was significantly higher when compared with saline placebo. After 12 min of cardiac arrest, including 8 min of CPR, seven of seven pigs in the vasopressin group, one of six pigs in the adrenaline group, but none of six placebo were successfully defibrillated. CONCLUSION: Both vasopressin and adrenaline produced significantly higher medullary and cortical adrenal gland perfusion during CPR than did a saline placebo; but vasopressin resulted in significantly higher medullary adrenal gland blood flow when compared with adrenaline.     

Effects of diltiazem on oxygen delivery and consumption after asphyxial cardiac arrest and resuscitation.

BACKGROUND AND METHODS: Calcium-channel blockers may attenuate vasospasm after transient ischemia and improve organ blood flow after resuscitation. Our aim was to assess the effect of diltiazem on systemic oxygen delivery and consumption, hemodynamics, electroencephalogram (EEG), and organ blood flow after restoration of spontaneous circulation. After a 3-min period of asphyxial cardiac arrest, 14 pigs (20 to 27 kg) were randomly allocated to treatment with either diltiazem (0.1 mg/kg bolus followed by an iv infusion of 0.025 mg/min/kg over 120 mins) or placebo, given at 5 mins after successful resuscitation. Organ blood flow was measured using tracer microspheres 120 mins after resumption of spontaneous circulation. RESULTS: Median systemic oxygen delivery index values at 30, 60, and 120 mins after restoration of spontaneous circulation were 18.2 mL/min/kg (range 14.8 to 20.7), 16.8 mL/min/kg (13.2 to 20.8), and 19.6 mL/min/kg (16.9 to 21.0), respectively, in the diltiazem group and 13.1 mL/min/kg (11.2 to 14.6), 11.9 mL/min/kg (10.3 to 13.3), and 14.7 mL/min/kg (11.4 to 17.2), respectively, in the control group (p less than .05 for all three comparisons). At the same points in time, median systemic oxygen consumption indices were 3.2 mL/min/kg (range 2.2 to 3.7), 2.1 mL/min/kg (1.9 to 3.0), and 2.6 mL/min/kg (1.8 to 3.8) in the diltiazem group and 2.8 mL/min/kg (2.1 to 4.0), 2.7 mL/min/kg (1.7 to 4.3), and 2.3 mL/min/kg (1.6 to 3.8) in the placebo group (NS). Diltiazem enhanced the postarrest recovery of EEG total power. Right and left cerebral blood flow 120 mins after restoration of spontaneous circulation was significantly (p less than .01) higher in the diltiazem group in comparison with the control group. CONCLUSIONS: Diltiazem causes an increase in systemic oxygen delivery index by promoting vasodilation, but it does not change systemic oxygen consumption index in comparison to placebo treatment. It may be that an impairment in local autoregulation and/or in oxidative metabolism at the cellular or subcellular level was the reason why diltiazem did not improve these derangements. The observed increase in cerebral blood flow and in EEG recovery may be beneficial to the brain after a period of asphyxia.     

Resuscitation from cardiac arrest with adrenaline/epinephrine or vasopressin: effects on intestinal mucosal tonometer pCO(2) during the postresuscitation period in rats

BACKGROUND: The use of vasopressin instead of adrenaline/epinephrine during resuscitation improves vital organ perfusion, but the effects on mesenteric perfusion following successful resuscitation are not fully evaluated. The present study was designed to compare the effects of vasopressin and adrenaline/epinephrine, given to rats during resuscitation from ventricular fibrillation, on to mesenteric ischaemia, as determined by intestinal mucosal tonometer pCO(2) during the postresuscitation period. METHODS AND RESULTS: Male Sprague-Dawley rats (n=28) were allocated randomly to receive vasopressin (0.8 U/kg) or adrenaline/epinephrine (90 microg/kg) after 5 min of ventricular fibrillation. Precordial chest compression was initiated 4 min after the start of ventricular fibrillation, continued for 4 min, and followed by defibrillation. Seven of 14 (vasopressin) and 12 of 14 (adrenaline/epinephrine) rats were successfully defibrillated (P=0.10, Fisher's exact test) and observed for 60 min. Intestinal mucosal tonometer pCO(2) measurements before cardiac arrest and 15, 30, and 60 min following return of spontaneous circulation were 47+/-3, 73+/-8, 63+/-7, and 56+/-6 mmHg in the vasopressin group and 48+/-5, 78+/-7, 67+/-6, and 62+/-6 mmHg in the adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and adrenaline/epinephrine). Right atrial hemoglobin oxygen saturations at these time points were 73+/-5, 51+/-12, 58+/-11, and 63+/-5% in the vasopressin group and 76+/-7, 44+/-10, 52+/-10 and 54+/-8% in the adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and adrenaline/epinephrine). CONCLUSIONS: We conclude that in this rat model the administration of vasopressin instead of adrenaline/epinephrine for CPR tends to be associated with lower resuscitation success, but less mesenteric ischaemia during the postresuscitation period in successfully resuscitated rats.     

Effect of extracorporeal membrane oxygenation on cerebral hemodynamics in newborn lambs.

BACKGROUND AND PURPOSE: Neurologic injury caused by changes in cerebral blood flow is a concern in infants treated with extracorporeal membrane oxygenation (ECMO). To investigate the hypothesis that cerebral hemodynamics would be influenced by bypass flow rates, eight ketamine anesthetized lambs (age range 1 to 8 days) had measurements of cerebral hemodynamics before and after institution of venoarterial bypass. METHODS: Cerebral blood flow (whole brain and regional) were measured using the radiolabeled microsphere technique. A left carotid artery catheter (placed without sacrificing the vessel) reference sample was used for calculation of brain blood flows. Arterial and venous (sagittal sinus) oxygen contents and blood gases were measured across the cerebral circulation. Cerebral oxygen consumption, oxygen delivery, and fractional oxygen extraction were calculated. Measurements were made pre-ECMO and after placement on venoarterial ECMO at flow rates of 50 and 100 mL/kg/min. In addition, four other lambs were studied at a flow rate of 150 mL/kg/min, and seven additional animals were used to address methodologic issues with the microsphere technique in this model. RESULTS: Cerebral blood flow and oxygen delivery significantly decreased, compared with control at both flow rates of 100 and 50 mL/kg/min (87.8 +/- 5.2 vs. 36.4 +/- 6.2; and 35.1 +/- 5.8 mL/100 g/min; 5.82 +/- 0.37 vs. 2.14 +/- 0.35; and 2.19 +/- 0.39 microM/100 g/min, respectively). Cerebral fractional oxygen extraction increased significantly at a flow of 50 mL/kg, and cerebral oxygen consumption decreased significantly at a flow of 100 mL/kg. At a flow rate of 150 mL/kg/min, cerebral hemodynamic variables did not differ from control measurements. CONCLUSIONS: These findings demonstrate that changes in cerebral blood flow and cerebral oxygen metabolism can occur in the newborn lamb with the initiation of ECMO, and that these changes are dependent on bypass flow rate.     

Revised resuscitation guidelines: adrenaline versus adrenaline/vasopressin in a pig model of cardiopulmonary resuscitation--a randomised, controlled trial

BACKGROUND: Synergistic effects of adrenaline (epinephrine) and vasopressin may be beneficial during cardiopulmonary resuscitation. However, it is unknown whether either adrenaline alone or an alternating administration of adrenaline and vasopressin is better for restoring vital organ perfusion following basic life support (BLS) according to the revised algorithm with a compression-to-ventilation (c/v) ratio of 30:2. MATERIAL AND METHODS: After 4min of ventricular fibrillation, and 6min of BLS with a c/v ratio of 30:2, 16 pigs were randomised to receive either 45microg/kg adrenaline, or alternating 45microg/kg adrenaline and 0.4U/kg vasopressin, respectively. RESULTS: Coronary perfusion pressure (mean+/-S.D.) 20 and 25min after cardiac arrest was 7+/-4 and 5+/-3mm Hg after adrenaline, and 25+/-2 and 14+/-3mm Hg after adrenaline/vasopressin (p<0.001 and <0.01 versus adrenaline), respectively. Cerebral perfusion pressure was 23+/-7 and 19+/-9mm Hg after adrenaline, and 40+/-10 and 33+/-7mm Hg after adrenaline/vasopressin (p<0.001 and <0.01 versus adrenaline), and cerebral blood flow was 30+/-10 and 27+/-11% of baseline after adrenaline, and 65+/-40 and 50+/-31% of baseline after adrenaline/vasopressin (p<0.05 versus adrenaline), respectively. Return of spontaneous circulation (ROSC) did not differ significantly between the adrenaline group (0/8) and the adrenaline/vasopressin group (3/8). CONCLUSION: Adrenaline/vasopressin resulted in higher coronary and cerebral perfusion pressures, and cerebral blood flow, while ROSC was comparable.     

Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury

OBJECTIVE: Two series of experiments were designed to evaluate whether early arginine vasopressin improves acute outcome following resuscitation from traumatic brain injury and severe hemorrhagic hypotension. DESIGN: Prospective randomized, blinded animal study. SETTING: University laboratory. SUBJECTS: Thirty-three swine. INTERVENTIONS: In series 1 (n = 19), after traumatic brain injury with hemorrhage and 12 mins of shock (mean arterial pressure approximately 20 mm Hg), survivors (n = 16) were initially resuscitated with 10 mL/kg crystalloid. After 30 mins, crystalloid and blood with either 0.1 unit x kg(-1) x hr(-1) arginine vasopressin or placebo was titrated to a mean arterial pressure target >or=60 mm Hg. After 90 mins, all received mannitol and the target was cerebral perfusion pressure >or=60 mm Hg. To test cerebrovascular function, 7.5% inhaled CO2 was administered periodically. In series 2 (n = 14), the identical protocol was followed except the shock period was 20 mins and survivors (n = 10) received a bolus of either arginine vasopressin (0.2 units/kg) or placebo during the initial fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: In series 1, by 300 mins after traumatic brain injury with arginine vasopressin (n = 8) vs. placebo (n = 8), the fluid and transfusion requirements were reduced (both p < .01), intracranial pressure was improved (11 +/- 1 vs. 23 +/- 2 mmHg; p < .0001), and the CO2-evoked intracranial pressure elevation was reduced (7 +/- 2 vs. 26 +/- 3 mm Hg, p < .001), suggesting improved compliance. In series 2, with arginine vasopressin vs. placebo, cerebral perfusion pressure was more rapidly corrected (p < .05). With arginine vasopressin, five of five animals survived 300 mins, whereas three of five placebo animals died. The survival time with placebo was 54 +/- 4 mins (p < .05 vs. arginine vasopressin). CONCLUSIONS: Early supplemental arginine vasopressin rapidly corrected cerebral perfusion pressure, improved cerebrovascular compliance, and prevented circulatory collapse during fluid resuscitation of hemorrhagic shock after traumatic brain injury.